Materials must meet demanding criteria in order to function well in a biocompatible role, where sustained intimate contact with a living organism is expected. Ophthalmic lenses must meet particularly demanding criteria, and materials from which lenses are made must therefore also possess a demanding combination of properties. Lens material must be sufficiently oxygen permeable to allow adequate oxygen to permeate through lenses to reach users' eyes. Lenses must be sufficiently physically robust to remain intact while worn in the user's eye, as well as during handling, installation, and removal. During wear, lens surfaces must be wettable, and must resist deposition of proteins, lipids, and other biological material. Lens material must also be highly transparent, and lenses that are soft or flexible are generally more comfortable to wear.
Some of the above characteristics are difficult to achieve simultaneously. Rigid ophthalmic lenses have good visual clarity and are generally sufficiently physically robust, but their high modulus makes them uncomfortable for some users to wear. Soft ophthalmic lenses have a lower modulus that makes them more comfortable to wear, but decreased modulus often comes at the expense of decreased tear strength. Moreover, soft ophthalmic lenses typically cover a larger area and conform closely to the contour of the surface of an eye than rigid ophthalmic lenses. Accordingly, soft ophthalmic lenses typically need to have sufficient oxygen permeability to avoid oxygen deprivation of wearers' eyes.
Ophthalmic lenses made of non-silicone hydrogels typically have moderate to high water content and, provided the lens is sufficiently thin, can be produced to have acceptable oxygen permeability along with desirable wettability. However, excellent oxygen permeability is difficult to attain with non-silicone hydrogels, and high water content hydrogels can be physically unstable, having a tendency to reduce in size with increases in temperature. In addition, thin lenses made from materials with high water content are also prone to dehydrate on the eye, which results in lower on-eye oxygen permeability and can also lead to serious clinical complications. For lathe cut lenses, which often have increased thickness compared to cast-molded lenses, oxygen transmissibility is often undesirably low.
Silicone hydrogels generally have higher oxygen permeability than non-silicone hydrogels, but high silicone content can result in increased modulus and poor surface properties that lead to poor wettability and deposition of biological material on lens surfaces. High silicone content material also tends to be difficult or impossible to lathe at or above room temperature, thereby making manufacture of ophthalmic lenses by lathing silicone hydrogel material impracticable. Silicone hydrogel material that has a Tg at or near room temperature may nonetheless be difficult or impossible to lathe at room temperature because cutting the silicone hydrogel with a lathe can heat the material being cut. Lowering silicone content typically results in decreased oxygen permeability.
Ophthalmic lenses made from silicone hydrogels can achieve an adequate, albeit not optimal, balance of surface wettability and resistance to deposition, modulus of elasticity, tear resistance, and oxygen permeability. However, manufacturing silicone hydrogels and lenses therefrom introduces problems that are difficult or expensive to overcome. Moreover, it can be difficult to simultaneously achieve high oxygen permeability, low modulus and high wettability in silicone hydrogels, and it can be difficult to achieve high water content in silicone hydrogels that are high enough in silicone content to have desirable oxygen permeability. Finally, hydrogel lenses that have high water content tend to suffer from high water loss rates that result in undesirable dehydration of both lenses and wearers' eyes.
Silicone-containing monomers and hydrophilic monomers, from which silicone hydrogels are typically made, tend to resist dissolution and form separate phases in polymerization reaction mixtures comprising relatively high concentrations of hydrophilic and silicone-containing monomers. Manufacture of silicone hydrogels is thus complicated by the tendency of polymerization reaction mixtures to separate into relatively hydrophilic and hydrophobic phases, which can negatively impact polymerization and silicone hydrogel polymerization products. Silicone-containing monomers are often chemically modified to form prepolymers or macromers with relatively hydrophilic substituents that can be used in higher proportions than silicone-containing true monomers. Such silicone-containing prepolymers and macromers can be mixed more readily with hydrophilic monomers, helping to avoid phase separation in polymerization reaction mixtures comprising relatively high concentrations of these silicone containing species.
U.S. Pat. No. 4,711,943 (the Harvey patent) discloses silicone hydrogels comprising modified silicone-containing monomers, the modified silicone-containing monomers comprising a urethane linkage. Harvey discloses silicone hydrogels having fantastic putative physical properties. One example of silicone hydrogels disclosed in Harvey purportedly has a fully hydrated water content of 50.3%, oxygen permeability of 43 Barrers, and an extraordinary modulus of elasticity of 1.6×10−6 dynes/cm2 (see Sample A, Harvey Table XII). However, this modulus value is not credible. Persons of ordinary skill in the art recognize that 1.6×10−6 dynes/cm2 is an absurdly low modulus value, approximately 12 to 14 orders of magnitude below a reasonable number. Accordingly, it is tempting to suggest that the drafter of the Harvey patent was confused about the sign on the exponent, and the modulus value should be 1.6×106 dynes/cm2. However, 1.6×106 dynes/cm2 (0.16 MPa) is a very low modulus value for a silicone hydrogel, especially one comprising 43.38% N-[tris(trimethylsiloxy)silylpropyl]methacrylamide (TSMAA), leading persons of ordinary skill to reasonably surmise that the absolute value of the modulus exponent is incorrect as well as the sign.
Further evidence that modulus values disclosed in the Harvey patent are unfounded is shown in many other tables, and particularly in Table XIX, where modulus values of about 1.9×10−10 dynes/cm2 are disclosed in silicone compositions containing 35% to 40% TSMAA. Such values are inconceivably low. Other spurious physical parameter values, including values that make more sense if signs on exponents are reversed, appear endemic to the Harvey patent. However, it is beyond the scope of this application to trouble shoot the surfeit of errors in the Harvey patent.
In summary, the Harvey patent discloses modulus values that defy belief by persons of ordinary skill in the art. Accordingly, modulus figures disclosed in Harvey are not credible. Nevertheless, Harvey discloses a silicone hydrogel embodiment with fully hydrated water content of 58.2% and oxygen permeability of 35.2 Barrers, and another silicone hydrogel embodiment with oxygen permeability of 58 and water content of 37.6%. These water content and oxygen permeability values are fully plausible.
U.S. Pat. No. 5,486,579 (the Lai patent) discloses silicone hydrogel compositions comprising silicone-containing monomers with urethane linkages. The silicone hydrogels disclosed in Lai have varied water content and modulus of elasticity that are adjusted by varying abundance of hydrophilic monomers, including N-vinyl pyrrolidone (NVP) and N,N-dimethyl acrylamide (DMA). Lai discloses silicone hydrogels with modulus values as low as 0.62 MPa (63 g/mm2) at 37% fully hydrated water content (Table 1), but does not disclose any fully hydrated water content above about 46% (Table 1), and no modulus below 0.62 MPa.
Interestingly, the Lai patent claims modulus values as low as 0.05 MPa (5 g/mm2 in claim 5 and 15), a remarkably low but not inconceivable value. However, Lai does not disclose to how a person of ordinary skill in the art might achieve such low modulus in silicone hydrogels. Moreover, it is not implicit that silicone hydrogel formulations such as those disclosed in Lai could achieve modulus values lower than those of the specific examples disclosed.
Conversely, the Lai patent suggests that silicone hydrogels preferably have oxygen permeability of Dk >60 Barrers (Lai column 6, lines 58-59). A person of ordinary skill in the art would recognize that Dk >60 Barrers is possibly an inherent quality in a silicone hydrogel composition such as disclosed in Lai, examples of which contain about 30%-47% TRIS (Lai columns 9 and 10). Lai does not, however, explicitly enable a person of ordinary skill in the art to make a silicone hydrogel with oxygen permeability >60 Barrers.
In summary, the Lai patent discloses silicone hydrogels with fully hydrated water content around 25% to 46% that also have modulus values of 0.62 MPa to 0.85 MPa (63 to 87 g/mm2). Lai does not disclose how a person of ordinary skill in the art can make a silicone hydrogel with a modulus below 0.62 MPa, and embodiments of hydrogels and processes for making hydrogels exemplified in Lai do not implicitly achieve the low modulus claimed in Lai claims 5 and 15. Lai arguably does implicitly disclose silicone hydrogel compositions with Dk >60 Barrers.
U.S. Pat. No. 6,649,722 (the Rosenzweig patent) discloses silicone hydrogel compositions that achieve relatively high oxygen permeability (Dk=117 Barrers) at moderately low water content (32%), and lower oxygen permeability (88 Barrers) at higher water content (46%). Rosenzweig discloses silicone hydrogels with water content as high as 53%, but does not disclose a Dk value for 53% water content silicone hydrogel. The Rosenzweig disclosure shows a loose inverse correlation between water content and oxygen permeability in the Rosenzweig silicone hydrogels. Rosenzweig also discloses numerous silicone hydrogels that comprise styrene or substituted styrene.
United States Patent Application No. 2006/0004165 (the Phelan application) discloses silicone hydrogel compositions that are prepared from reaction mixtures comprising urethane macromers and styrene or substituted styrene monomers. Examples of silicone hydrogel material disclosed in Phelan have oxygen permeability ≧65 Barrers and glass transition temperatures (Tg) in a 60-68° C. range. Interestingly, Phelan discloses room temperature lathability and associated property Tg of 60° to 68° in silicone hydrogels comprising styrene or substituted styrenes that are remarkably similar to silicone hydrogels comprising styrene or substituted styrene disclosed in Rosenzweig.
Collectively, prior art silicone hydrogels have not been able to achieve fully hydrated water content ≧60%. Moreover, prior art hydrogels have not achieved lathability at or above room temperature without the use of urethane macromers and styrene monomers. In addition, prior art references have not disclosed silicone hydrogels with combined physical properties of water content >50%, oxygen permeability >45 Barrers, contact angle <90°, and modulus <1.0 MPa.